Population-based Assessment of Cardiometabolic-related Diagnoses in Youth With Klinefelter Syndrome: A PEDSnet Study

J Clin Endocrinol Metab. 2022 Apr 19;107(5):e1850-e1859. doi: 10.1210/clinem/dgac056.


Context: Diabetes and cardiovascular diseases are common among men with Klinefelter syndrome (KS) and contribute to high morbidity and mortality.

Objective: To determine if cardiometabolic-related diagnoses are more prevalent among youth with KS than matched controls in a large population-based cohort.

Methods: Secondary data analysis of electronic health records from 6 pediatric institutions in the United States (PEDSnet). Patients included all youth with KS in the database (n = 1080) and 4497 youth without KS matched for sex, age (mean 13 years at last encounter), year of birth, race, ethnicity, insurance, site, and duration of care (mean 7 years). The main outcome measures were prevalence of 5 cardiometabolic-related outcomes: overweight/obesity, dyslipidemia, dysglycemia, hypertension, and liver dysfunction.

Results: The odds of overweight/obesity (OR 1.6; 95% CI 1.4-1.8), dyslipidemia (3.0; 2.2-3.9), and liver dysfunction (2.0; 1.6-2.5) were all higher in KS than in controls. Adjusting for covariates (obesity, testosterone treatment, and antipsychotic use) attenuated the effect of KS on these outcomes; however, boys with KS still had 45% greater odds of overweight/obesity (95% CI 1.2-1.7) and 70% greater odds of liver dysfunction (95% CI 1.3-2.2) than controls, and both dyslipidemia (1.6; 1.1-2.4) and dysglycemia (1.8; 1.1-3.2) were higher in KS but of borderline statistical significance when accounting for multiple comparisons. The odds of hypertension were not different between groups.

Conclusion: This large, population-based cohort of youth with KS had a higher odds of most cardiometabolic-related diagnoses than matched controls.

Keywords: Klinefelter syndrome; PEDSnet; cardiometabolic; diabetes; population health; sex chromosome aneuploidy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Cardiovascular Diseases* / diagnosis
  • Cardiovascular Diseases* / epidemiology
  • Cardiovascular Diseases* / etiology
  • Child
  • Dyslipidemias* / epidemiology
  • Female
  • Humans
  • Hypertension*
  • Klinefelter Syndrome* / complications
  • Klinefelter Syndrome* / diagnosis
  • Klinefelter Syndrome* / epidemiology
  • Male
  • Obesity / complications
  • Obesity / epidemiology
  • Overweight